We have detected both high (HMW) and low (LMW) molecular weight enkephalin-like peptides in sympathetic ganglia and adrenal glands. In deafferented adrenal glands, the content of LMW enkephalin-like peptides is reduced. Also, primary cultures of chromaffin cells contain little or no LMW but HMW forms are abundant. These results suggest that LMW forms may be located in afferent axons and the HMW forms in chromaffin cells. Conversely, one can also argue that LMW forms are produced by nerve impulses. The HMW forms contain the enkephalin sequence, probably at their c-termini; these peptides may function as pro-enkephalins. Since similar LMW enkephalin-like peptides are present in blood, it is conceivable that chromaffin cells may release the LMW peptides into blood where they function as hormones. We have studied the content of HMW and LMW enkephalin-like peptides in tissues of spontaneously hypotensive rats (SHR) and found that LMW peptides are reduced in peripheral but not in brain tissue. The results suggest that enkephalin-like peptides in sympathetic ganglia and adrenal glands may play some role in regulation of vascular tone.